AJM Theme Issue: GI and Nutrition
Review
Selective Serotonin Reuptake Inhibitors and Risk of Upper GI Bleeding: Confusion or Confounding?

https://doi.org/10.1016/j.amjmed.2005.11.006Get rights and content

Abstract

Background

Selective serotonin reuptake inhibitors (SSRIs) represent a relatively new class of antidepressants. Several studies have reported bleeding disorders associated with the use of SSRIs, which are considered the result of a decrease in platelet serotonin leading to a defect in platelet aggregation. To what extent the use of SSRIs increases the risk of gastrointestinal bleeding is unclear.

Methods

A comprehensive literature search for studies addressing SSRI use and upper gastrointestinal tract bleeding (UGIB) was conducted using Medline, EMBASE, and Cochrane databases with a recursive manual reference search up to May 2005. Any observational and interventional studies were systematically reviewed, and critical appraisal was conducted on available studies.

Results

Published clinical evidence on the relationship between SSRI use and gastrointestinal bleeding is limited to observational studies without any clinical trials. Three cohort studies and one case-control study met inclusion criteria. These studies combined different affinity SSRIs in the class and had differing control groups with conflicting conclusions. Both a cohort study and a case-control study investigating the concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin found that combined use with an SSRI increased the risk of UGIB.

Conclusions

Only a few epidemiology studies have investigated the association between SSRIs and UGIB. They provide weak evidence to support the hypothesis of a link between SSRIs and UGIB at a population level. Available evidence shows that concurrent use of NSAIDs or aspirin with SSRIs greatly increases the risk of UGIB. The preventive strategy should be considered in those SSRI users at high risk, especially the elderly or those with a history of UGIB and taking nonselective NSAIDs or aspirin.

Section snippets

Methods

MEDLINE, EMBASE, the Cochrane Controlled Trials register, and the Food and Drug Administration (FDA) website were searched for studies addressing SSRI use and UGIB in humans from 1980 to May 2005, and the literature was systematically reviewed.

Keywords used were “SSRI(s)” or “selective serotonin reuptake inhibitor (s)” and “bleeding” or “hemorrhage”; different commonly used brand names of SSRIs including fluoxetine (Prozac, Eli Lilly and Company, Indianapolis, IN), sertraline (Zoloft [Pfizer

Selective Serotonin Reuptake Inhibitors and Upper Gastrointestinal Bleeding

Published clinical evidence on the relationship between SSRI use and GI bleeding is limited to observational studies without any clinical trials. Thirty-eight articles including case reports and reviews related to SSRI use and bleeding were initially identified and retrieved. Only 6 articles (4 cohort and 2 case-control studies) that addressed GI bleeding met inclusion criteria.14, 20, 21, 22, 23, 24 Two of them were in letter format20 or abstract form.24 One cohort study, which concluded no

Mechanisms of Selective Serotonin Reuptake Inhibitors Increase Bleeding Risk

The concentration of serotonin (5-HT) in platelets is critical for maintaining platelet hemostatic function; serotonin released from the platelet potentiates platelet aggregation induced by adenosine diphosphate or thrombin.29 In principle, SSRIs can impair hemostatic function because serotonin is not synthesized in platelets but taken up from the circulation by serotonin transporters on the platelets.30 SSRIs at therapeutic doses block this reuptake of serotonin by platelets leading to a

Conclusions

Only a few epidemiology studies have investigated the association between SSRIs and UGIB. They provide weak evidence to support a link between SSRIs and UGIB at a population level. SSRIs may precipitate GI bleeding in certain circumstances, such as in those with a preexisting hemostatic defect or who are taking concomitant drugs that cause GI injury. Available evidence shows that concurrent use of NSAIDs or low-dose aspirin with SSRIs greatly increases the risk of UGIB. It is important to

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